Aortic Root Abscess Presenting As Chest Pain and Ischemic EKG Changes: Importance of Timely Diagnosis.

The occurrence of perivalvular abscess, a purulent infection that affects the myocardium and endocardium of natural or artificial valve tissues, can result from either the spread of bacteria from a distant source via bacteremia, or from the expansion of an existing infectious cardiac focus, such as infective endocarditis (IE). The aortic abscess should be suspected in patients with infective endocarditis who fail to improve despite being on appropriate antibiotics. Sometimes aortic abscesses can present as PR interval lengthening or heart block due to the extension of infection. We present an atypical presentation of aortic root abscess with chest pain and ischemic EKG changes. A 45-year-old intravenous drug user presented with chest pain episodes with EKG showing ST depression in V2-V6 and ST elevation in avR. The coronary angiographic study showed no significant coronary artery disease, but the patient complained of chest pain. Transthoracic echo in the catheterization lab showed severe aortic regurgitation. The patient became hemodynamically unstable, worsened his respiratory status, and had to be intubated. He had a bedside transesophageal echo that revealed an aortic root abscess. The patient's condition continued deteriorating, and he passed away the same day. This case focuses on the timely diagnosis of aortic root abscess, and Transesophageal echocardiography (TEE) is the gold standard for diagnosing aortic root abscesses. This case also focuses on keeping perivalvular abscess among our differentials in a patient presenting with chest pain and abnormal EKG, especially in a high-risk population.

Spontaneous Coronary Artery Dissection of an Anomalous Right Coronary Artery in a Young Male.

Spontaneous coronary artery dissection (SCAD) is a tear in the coronary artery layers that presents clinically as an acute coronary syndrome (ACS), ventricular arrhythmias, or sudden cardiac death (SCD). It is uncommon for young healthy males with no comorbid conditions to have SCAD. We report an interesting case of SCAD in an anomalous right coronary artery (RCA) in a young 33-year-old male. The patient presented with episodes of midsternal chest pain and had elevated troponins on laboratory workup. A left heart catheterization revealed anomalous RCA, originating from the left aortic sinus. The left heart catheterization also demonstrated a SCAD of the anomalous RCA. Cardiothoracic surgery was consulted, and the patient had placement of saphenous vein graft to the proximal RCA. While this patient's presentation of ACS in the setting of SCAD is relatively common, it was atypical due to gender and lack of precipitating stressors. One of the risk factors this patient did have was the anomalous RCA arising from the left aortic sinus. There is scarce literature involving guidance for therapeutic intervention for RCA ostial lesion, let alone an anomalous one. Although coronary artery bypass grafting (CABG) remains the most clinically sound decision, in this case, further development of guidelines for RCA lesions would aid in decision-making.

The Self Sabotaging Vessel: A Case Report and Literature Review of Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is a very rare cause of acute coronary syndrome. Despite the recent advances in the management of cardiovascular diseases, the diagnoses and management of SCAD remain a dilemma. It has been described to majorly affect females of childbearing age, immediately post-partum or on oral contraceptives. Recent cases have also identified underlying connective tissue disease as a risk factor. Since its discovery, only a limited number of cases affecting males have been reported in the literature. This makes our case unique. In this, we present a 31-year-old male without any traditional risk factors who presented with atypical chest pain. Electrocardiogram showed ST-segment changes with echocardiogram revealing apical left ventricular akinesis. A diagnostic left heart catheterization showed multiple lumens in the distal left anterior descending artery (LAD). The patient was managed conservatively and discharged home on guideline-directed medical therapy.

Personal Health Records: Beneficial or Burdensome for Patients and Healthcare Providers?

Personal health records (PHRs) have been mandated to be made available to patients to provide increased access to medical care information, encourage participation in healthcare decision making, and enable correction of errors within medical records. The purpose of this study was to analyze the usefulness of PHRs from the perspectives of patients and providers. The methodology of this qualitative study was a literature review using 34 articles. PHRs are powerful tools for patients and healthcare providers. Better healthcare results and correction of medical records have been shown to be positive outcomes of the use of PHRs. PHRs have also been shown to be difficult for patients to use and understand, and providers had concerns about correct information transferring to the portals and patients eliminating information from the record. Concerns regarding patient understanding of medical records, legal liability, and the response time required of providers were also identified. For the PHR to succeed in the US healthcare system, assurance that the information will be protected, useful, and easily accessed is necessary.

The ζ isoform of diacylglycerol kinase plays a predominant role in regulatory T cell development and TCR-mediated ras signaling.

Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA) and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms are DGKα and DGKζ, and deletion of the genes encoding either isoform enhances DAG-mediated signaling. We found that DGKζ, but not DGKα, suppressed the development of natural regulatory T (T(reg)) cells and predominantly mediated Ras and Akt signaling downstream of the TCR. The differential functions of DGKα and DGKζ were not attributable to differences in protein abundance in T cells or in their localization to the contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG-mediated activator of Ras signaling, associated to a greater extent with DGKζ than with DGKα; however, in silico modeling of TCR-stimulated Ras activation suggested that a difference in RasGRP1 binding affinity was not sufficient to cause differences in the functions of each DGK isoform. Rather, the model suggested that a greater catalytic rate for DGKζ than for DGKα might lead to DGKζ exhibiting increased suppression of Ras-mediated signals compared to DGKα. Consistent with this notion, experimental studies demonstrated that DGKζ was more effective than DGKα at catalyzing the metabolism of DAG to PA after TCR stimulation. The enhanced effective enzymatic production of PA by DGKζ is therefore one possible mechanism underlying the dominant functions of DGKζ in modulating T(reg) cell development.

EnP1, a microsporidian spore wall protein that enables spores to adhere to and infect host cells in vitro.

Microsporidia are spore-forming fungal pathogens that require the intracellular environment of host cells for propagation. We have shown that spores of the genus Encephalitozoon adhere to host cell surface glycosaminoglycans (GAGs) in vitro and that this adherence serves to modulate the infection process. In this study, a spore wall protein (EnP1; Encephalitozoon cuniculi ECU01_0820) from E. cuniculi and Encephalitozoon intestinalis is found to interact with the host cell surface. Analysis of the amino acid sequence reveals multiple heparin-binding motifs, which are known to interact with extracellular matrices. Both recombinant EnP1 protein and purified EnP1 antibody inhibit spore adherence, resulting in decreased host cell infection. Furthermore, when the N-terminal heparin-binding motif is deleted by site-directed mutagenesis, inhibition of adherence is ablated. Our transmission immunoelectron microscopy reveals that EnP1 is embedded in the microsporidial endospore and exospore and is found in high abundance in the polar sac/anchoring disk region, an area from which the everting polar tube is released. Finally, by using a host cell binding assay, EnP1 is shown to bind host cell surfaces but not to those that lack surface GAGs. Collectively, these data show that given its expression in both the endospore and the exospore, EnP1 is a microsporidian cell wall protein that may function both in a structural capacity and in modulating in vitro host cell adherence and infection.

Cost-effectiveness strategies to treat osteoporosis in elderly women.

BACKGROUND: Comparing the cost-effectiveness of various antiosteoporotic drugs has not been defined. METHODS: We determined the cost-effectiveness of calcitonin, raloxifene, bisphosphates and PTH in a base-case cohort of women aged 65 or older with osteoporosis. After bone densitometry, women were stratified into groups of treatment or no treatment. Our outcome goal was a value of dollars 100,000 or less per quality-adjusted life years (QALY). A sensitivity analysis varied nonvertebral fracture reduction and compliance between the two most effective strategies to test various cost per QALY thresholds. RESULTS: Bisphosphonates displayed the most favorable incremental cost saving and prevented more fractures in our base-case analysis. In a sensitivity analysis, virtually all values of bisphosphonates were under dollars 100,000 per QALY and parathyroid hormone (PTH) was between dollars 100,000 and dollars 200,000 per QALY. CONCLUSIONS: Only bisphosphonates are cost-effective for fracture prevention in osteoporotic women aged 65 or older and this economic advantage is also maintained in subsets who have a lower relative risk of future fracture.

Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A.

Attachment of positively charged, amine-containing residues such as 4-amino-4-deoxy-l-arabinose (l-Ara4N) and phosphoethanolamine (pEtN) to Escherichia coli and Salmonella typhimurium lipid A is required for resistance to the cationic antimicrobial peptide, polymyxin. In an attempt to discover additional lipid A modifications important for polymyxin resistance, we generated polymyxin-sensitive mutants of an E. coli pmrA(C) strain, WD101. A subset of polymyxin-sensitive mutants produced a lipid A that lacked both the 3'-acyloxyacyl-linked myristate (C(14)) and l-Ara4N, even though the necessary enzymatic machinery required to synthesize l-Ara4N-modified lipid A was present. Inactivation of lpxM in both E. coli and S. typhimurium resulted in the loss of l-Ara4N addition, as well as, increased sensitivity to polymyxin. However, decoration of the lipid A phosphate groups with pEtN residues was not effected in lpxM mutants. In summary, we demonstrate that attachment of l-Ara4N to the phosphate groups of lipid A and the subsequent resistance to polymyxin is dependent upon the presence of the secondary linked myristoyl group.

Transgenic tobacco and apple plants expressing biotin-binding proteins are resistant to two cosmopolitan insect pests, potato tuber moth and lightbrown apple moth, respectively.

Tobacco (Nicotiana tabacum cv. Samsun) and apple (Malus x domestica cv. Royal Gala) plants expressing avidin or strepavidin were produced using Agrobacterium tumefaciens-mediated transformation. ELISA assays showed that avidin expression ranged from 3.1 to 4.6 microM in tobacco and from 1.9 to 11.2 microM in apple and streptavidin expression ranged from 11.4 to 24.5 microM in tobacco and from 0.4 to 14.6 microM in apple. Expressed at these levels, both biotin-binding proteins conferred a high level of insect resistance on transformed tobacco plants to larval potato tuber moth (PTM), Phthorimaea operculella (Zeller) (fam. Gelechiidae) and on apple plants to larvae of the lightbrown apple moth (LBAM) Epiphyas postvittana (Walker) (fam. Tortricidae). More than 90% of PTM larvae died on tobacco plants expressing either avidin or streptavidin genes within 9 days of inoculation. Mortality of LBAM larvae was significantly higher (P < 0.05) on three avidin-expressing (89.6, 84.9 and 80.1%) and two streptavidin-expressing (90 and 82.5%) apple plant lines than on non-transformed control plants (14.1%) after 21 days. Weight of LBAM larvae was also significantly reduced by feeding on all apple shoots expressing avidin and on apple shoots expressing streptavidin at levels of 3.8 microM and above.

Avidin expressed in transgenic tobacco leaves confers resistance to two noctuid pests, Helicoverpa armigera and Spodoptera litura.

Fertile transgenic tobacco plants with leaves expressing avidin in the vacuole have been produced and shown to halt growth and cause mortality in larvae of two noctuid lepidopterans, Helicoverpa armigera and Spodoptera litura. Late first instar H. armigera larvae and neonate (< 12-h-old) S. litura larvae placed on leaves excised from T0 tobacco expressing avidin at 3.1-4.6 microM (micromoles/kg of fresh leaf tissue) had very poor growth over their first 8 days on the leaves, significant numbers had died by days 11 or 12 and all were dead by day 22 (H. armigera) or day 25 (S. litura). Similar results were obtained when late first instar H. armigera larvae were placed on leaves from T1 plants expressing avidin at six different average concentrations, ranging from 3.7 to 17.3 microM. Two larvae on the lowest expressing leaves survived to pupation, but there was total mortality among the other groups and no relationship between avidin concentration and the effects on the larvae. Synergistic effects between avidin-expressing tobacco plants and a purified Bt toxin, Cry1Ba, were demonstrated. Late instar H. armigera larvae fed with leaves from T2 plants expressing avidin at average concentrations of either <5.3 or > 12.9 microM, and painted with Cry1Ba protein at a rate equivalent to an expression level of 0.5% of total leaf protein, died significantly faster than larvae given either of the two treatments alone. Larvae fed with avidin-expressing leaves painted with the protease inhibitor, aprotinin, at a rate equivalent to 1% of total leaf protein had mortality similar to those given avidin-leaves alone. There was no evidence of antagonism between these two proteins.

Expression of biotin-binding proteins, avidin and streptavidin, in plant tissues using plant vacuolar targeting sequences.

Tobacco plants have been developed which constitutively express high levels of the biotin-binding proteins, avidin and streptavidin. These plants were phenotypically normal and produced fertile pollen and seeds. The transgene was expressed and its product located in the vacuoles of most cell types in the plants. Targeting was achieved by use of N-terminal vacuolar targeting sequences derived from potato proteinase inhibitors which are known to target constitutively to vacuoles in potato tubers and, under wound-induction, in tomato leaves. Avidin was located in protein body-like structures within the vacuole and transgene protein levels remained relatively constant throughout the lifetime of the leaf. We describe two chimeric constructs with similar levels of expression. One comprised a potato proteinase inhibitor I signal peptide cDNA sequence attached to an avidin cDNA and the second a potato proteinase inhibitor II signal peptide genomic sequence (including an intron) attached to a core streptavidin synthetic sequence. We were unable to regenerate plants when transformation used constructs lacking the targeting sequences. The highest levels observed (up to 1.5% of total leaf protein) confirm the vacuole as the organelle of choice for stable storage of plant-toxic transgene products. The efficient targeting of these proteins did not result in any measured changes in plant biotin metabolism.